The role of immunologic mechanisms in the perpetuation of chronic viral hepatitis is being studied and the effects of therapies for chronic viral hepatitis on the immune system are being evaluated. Patients with chronic type B hepatitis have normal or only slightly diminished immunologic function as assessed by standard, non-specific assays (delayed hypersensitivity skin tests, lymphocyte transformation in response to non-specific mitogens, in vitro production of immunoglobulin by B cells, and the absolute numbers of B cells and T cell subsets). Peripheral blood mononuclear cells from patients with chronic type B hepatitis produce low amounts of alpha interferon in response to challenge with infectious virus, but produce normal amounts of gamma interferon in response to typical inducers. In addition, peripheral blood mononuclear cells of patients with chronic type B hepatitis do not respond in vitro to low doses of alpha interferon with a normal augmentation of immunoglobulin synthesis. Furthermore, treatment with alpha interferon leads to a further decrease in immunoglobulin production by B cells in vitro; a decrease that appears to be due to a direct effect of interferon on B cells. The density and affinity of receptors for alpha interferon on peripheral blood mononuclear cells from normal subjects and patients with chronic type B hepatitis are similar. Administration of interferon in vitro or in vivo leads to a decrease in interferon receptor binding; this decrease in binding appears to be due to a decrease in receptor affinity rather than density.